[go: up one dir, main page]

WO1998043555A1 - Systeme intravesical de liberation de medicaments - Google Patents

Systeme intravesical de liberation de medicaments Download PDF

Info

Publication number
WO1998043555A1
WO1998043555A1 PCT/US1998/006445 US9806445W WO9843555A1 WO 1998043555 A1 WO1998043555 A1 WO 1998043555A1 US 9806445 W US9806445 W US 9806445W WO 9843555 A1 WO9843555 A1 WO 9843555A1
Authority
WO
WIPO (PCT)
Prior art keywords
preparation according
active ingredient
bladder
preparation
bioerodible
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US1998/006445
Other languages
English (en)
Inventor
Thomas B. Ottoboni
Ronald K. Yamamoto
Stanley R. Conston
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Point Biomedical Corp
Original Assignee
Point Biomedical Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Point Biomedical Corp filed Critical Point Biomedical Corp
Priority to CA002285591A priority Critical patent/CA2285591A1/fr
Priority to DE19882286T priority patent/DE19882286T1/de
Priority to JP54197098A priority patent/JP2001519787A/ja
Priority to AU68764/98A priority patent/AU6876498A/en
Priority to EP98914404A priority patent/EP0971641A4/fr
Priority to GB9923410A priority patent/GB2338414B/en
Priority to KR1019997009105A priority patent/KR20010006027A/ko
Publication of WO1998043555A1 publication Critical patent/WO1998043555A1/fr
Anticipated expiration legal-status Critical
Priority to NO994837A priority patent/NO994837L/no
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)

Definitions

  • the invention is directed to a system for the controlled and sustained delivery of therapeutic agents to the human bladder.
  • the drug doxorubicin is instilled directly into the bladder.
  • a mycobacterium Bacillus Calmette-Guerin, is also administered intravesically for treatment of carcinoma located in the bladder.
  • DMSO is instilled intravesically to provide symptomatic relief.
  • the anticholinergic drug oxybutynin chloride has been reported to have been used.
  • a sustained or controlled delivery device that is capable of delivery of the drug for an extended period of time, preferably one week or longer, with the device biodegrading or bioeroding over time to clear the bladder .
  • the invention provides a bioerodible, sustained- release preparation for placement into the bladder through the urethra.
  • the preparation may have a specific gravity less than or equal to that of the specific gravity range of human urine.
  • the preparation comprises a pharmaceutically active ingredient and at least one bioerodible, pharmaceutically acceptable carrier, which is capable of sustaining delivery of the active ingredient within the bladder and is bioerodible and excretable without blockage of the urinary tract.
  • Fig. 1 shows a preferred device according to the invention comprising a reservoir with a backing material
  • Fig. 2 shows a preferred device according to the invention comprising a reservoir with an adhesive coating
  • Fig. 3 shows an embodiment or device of the invention comprising a randomly oriented filament network
  • Fig. 4 shows an expanded view of one end of a filament, showing a segmented structure
  • Fig. 5 shows a preferred device according to the invention comprising a filament network having multiple segments which form a spherical cage.
  • Fig. 6 shows the rate of release of oxybutynin from a gel-in-place system in simulated urine solutions at pH 5.7 , 6.2 and 6.7.
  • Fig. 7 shows the rate of release of oxybutynin from two gels of different surface areas.
  • Fig. 8 shows the rate of release of oxybutynin from two gels having concentration of 3% and 1% oxybutynin.
  • Fig. 9 shows the rate of release of oxybutynin from gels having 3%, 6.25%, 12.5% and no oleic acid as a release rate modifier.
  • a bioerodible carrier according to the present invention means a carrier which is readily dissolved, eroded, or is subject to degradation in the bladder.
  • the carrier material according to the present invention does not substantially decompose, disperse, disintegrate or dissolve in the bladder until most of the drug has been released.
  • portions of the device will decompose, disperse, disintegrate or dissolve in a controlled manner so as to provide a controlled release of the drug contained in the decomposing portions.
  • Many carrier materials which are suitable for these embodiments are natural products, such as keratin, salol, triglycerides, fatty acids, lipids, latexes, as well as derivatives of natural products such as modified collagens, modified gelatins, regenerated proteins, celluloses, cellulose derivatives, salts of cellulose derivatives, alkaline or alkaline earth salts of cellulose acetate phthalate, ammonium salts of hydroxypropyl methyl cellulose phthalate, polysaccharides, synthetic polymers, such as, polyglycolic acid and derivatives of polyethylene glycol, polycaprolactone, polylactic acid, and copolymers thereof; materials such as starch, fatty alcohols, alginate polymers, albumin, calcium caseinate, calcium polypectate or gellan gum.
  • the carrier for the active ingredient may made by any number of methods known in the art for forming materials which contain medicaments.
  • a filament can be made with a centrifugal extrusion device or by coextrusion.
  • the filament texture is preferably a porous, open cell foam. Filaments may also be made by interfacial polymerization processes, known in the art, for example, for the manufacture of nylon.
  • the filament may be formed into random or regular coils, hoops, spheres, and the like.
  • Production by extrusion also enables the changing of the amount of the drug contained in the filament along the length of the filament, thereby allowing control of the dosage delivered in the bladder.
  • Extrusion also enables the containment of the drug in one portion of the filament and the use of one or more additional drugs or an alternate formulation of the same drug, in other portions of the filament for the same purpose.
  • the filament may contain two or more incompatible drugs in spatially distinct portions of the filament.
  • the drugs may also be encapsulated in the carrier.
  • the time release of the drug may be controlled by diffusion from the carrier and/or erosion of the carrier, which simultaneously releases the drug.
  • the bioerosion mechanism may be controlled by serially degrading segments of a filament. This may be accomplished, for example, by providing an outer layer of slowly bioerodible material with a core of rapidly bioerodible material containing the drug. Thus the exposed ends of the core will preferentially bioerode . At various points along the filament, weakened portions may be provided by which an outer layer may be detached once the core has been bioeroded, thereby causing the filament to be eroded in segments starting from the exposed ends .
  • the carrier materials may be formed in the desired shape or formed into sheets and cut into the appropriate form.
  • the carrier material will be typically one of two types.
  • One type bioerodes rather uniformly over time, so that the bioerosion of the carrier is also the primary mechanism for releasing the drug into the bladder.
  • the second type is a material which essentially remains intact during a substantial portion of the release period of the drug.
  • the mechanism of release of the drug is by diffusion or other mechanism which does not require the carrier to be concurrently bioeroded. However, in such cases, shortly after the drug has been depleted from the carrier, erosion should proceed in order to avoid the necessity of removing the device from the bladder.
  • the sustained delivery of the drug into the bladder will be for an extended period, longer than about three days and preferably, at least about one week.
  • the drug be delivered over a period up to about one month.
  • the carrier materials, containing or impregnated with the drug may have a specific gravity less than or equal to that of urine, which is normally about 1.005 gm/ml to 1.033 gm/ml at 25°C. This allows the device to be neutrally buoyant or float in the urine of the bladder to minimize the occurrence of blockage of the urethra.
  • a preferred embodiment of the delivery system is a flowable gel or set-in-place system that can be introduced into the bladder via a cannula.
  • set-in- place it is meant that the gel sets when introduced into the bladder.
  • the drug is dispersed or placed in a carrier (microsphere, liposome, emulsion, etc.) which in turn is dispersed in a gel-forming system, such as gellan gum, a polysaccharide derived fermentation of Pseudomonas elodea, available as Gelrite ® from Kelco. Solutions of this material gel when contacted with an ionic environment, which, in this case, is the urine in the bladder.
  • the preferred gel is an ionic gel-in-place type, such as gellan gum.
  • the retention mechanism is the buoyancy of the device, so its specific gravity must be less than or equal to that of human urine.
  • the ionic strength of the urine causes, for example, a solution of gellan gum to gel. Since oils have a density less than 1 gm/ml, a lipid emulsion component of the gel has a density less than 1.0 gm/ml.
  • the combination of the gel, having a density approximately equal to the surrounding medium, and a lipid, having a density less than 1.0 gm/ml affords a device with a net density less than the surrounding medium.
  • the gellan gum will slowly solubilize into the urine and be excreted, as will the lipid droplets.
  • the gelling system will preferably contain, in addition to the phase changing component (gellan, gum, alginate, CMC, polyacrylic acid, carboxymethyl chitosan, and the like), a rheology modifier.
  • This modifier will be a water-soluble high molecular weight polymer such as polyethylene oxide, PVP, dextran, dextrose, PEO/PVP copolymers, hyaluronic acid, hydroxyethyl cellulose, polyacrylamide, PVA, chitosan, gelatin or other high molecular weight water-soluble polymers.
  • the molecular weight of the rheology modifier is preferably in the range of about 10 5 -10 7 daltons .
  • the drug formulation is typically introduced into the lipid phase by mixing a salt form of the drug in water in the oil phase and increasing the pH. Deprotonation of the drug causes selective partition into the lipid phase, then the remainder of the components (the gelling component) are added. Alternatively, an un-ionized form of the drug is dissolved in the lipid phase, the release modifier is added, then the mixture is emulsified. The remaining components are then added.
  • the second preferred embodiment of a delivery system is a device physically capable of being retained in the bladder without blocking the urinary tract .
  • These devices are retained in the bladder by their shape such as a filament.
  • These systems must be formed from a bioerodible polymer that will reliably release drug over the predefined period of time and completely erode during that period. It is not necessary that this type of device have a density less than human urine.
  • At least one surface of the device may be coated with a mucoadhesive in order that the device adhere to the wall of the bladder.
  • Mucoadhesive coated microspheres are preferred.
  • mucoadhesives may be selected from a number of known synthetic, naturally-occurring or modified naturally-occurring substances which exhibit of tackiness.
  • the adhesive must be biocompatible, that is, nontoxic and/or inert, within the bladder. The adhesive will also be compatible with the material forming the carrier, as well as the drug.
  • Substances appropriate for use as mucoadhesives include, but are not limited to, carboxymethyl and hydroxypropyl methyl cellulose, and other cellulose derivatives; tragacanth, caraya, locust bean and other synthetic and naturally gums such as algin, chitosan, starches, pectins, and naturally- occurring resins, polyvinyl pyrrolidone, polyvinyl alcohol, and polyacrylic acid.
  • a device consisting of a drug reservoir 10 having a backing 12 bearing a mucoadhesive 11 on the back surface.
  • Fig. 2 shows a device according to the invention comprising a reservoir 13 to which is directly applied the mucoadhesive coating 14 so that the device may be attached to the wall of the bladder.
  • Fig. 3 shows a randomly oriented filament network 17 containing the drug.
  • This filament may be saturated with the drug, and may have a coating to control diffusion rate.
  • the filament may also be segmented.
  • Fig. 4 a view of an end of a segmented filament is shown.
  • the drug is shown to be contained within an axial drug reservoir 18 in the filament.
  • the network comprises segments 19 with erodible linking sections between the segments which allow the segments to detach as the drug reservoir is depleted within that segment .
  • Fig. 5 shows another network of filaments forming a spherical cage 20.
  • the devices containing the drug are insertable into the bladder through the urethra by a catheter.
  • the devices are preferably made of flexible or gel-like material so that they may be coiled or compressed to fit through a catheter of sufficient size.
  • the devices Upon being released from the catheter, the devices will have a sufficient shape memory to uncoil or expand into the shapes shown, for example, in the accompanying figures.
  • the devices per se will not be drawn into the urethra to cause blockage, but will be retained within the bladder for an extended period of time.
  • the mucoadhesive surface will eventually contact the bladder wall, thus achieving the desired implantation.
  • Drugs for urge incontinence include dicyclomine, desmopressin, oxybutynin, estrogen, terodiline, propantheline, doxepin, imipramine and flavoxate.
  • Other drugs include phenylpropanolamine, terazosin, praxosin, pseudoephedrine and bethanechol .
  • Oxybutynin and impranine are the two most widely used for urge incontinence and are preferred.
  • doxorubicin is preferred.
  • Bacillus Calmette-Guerin a mycobacterium, may be utilized for treatment of carcinoma in situ of the bladder.
  • DMSO or an anesthetic agent may be utilized for treatment of interstitial cystitis.
  • any drug may be utilized for the treatment of any condition related to the bladder or urethral tract, including urge incontinence, cancer, infections, inflammation, and the like.
  • the dosages utilized will depend upon the protocol required for the treatment of the particular condition and the patient. Particularly by use of filaments, variation in dosages is readily available since it is merely a case of using a longer or shorter length.
  • the drug will be combined with a carrier and, optionally, a release modifier which alters the release of the drug into bladder.
  • Typical carriers include corn oil, soybean oil, canola oil, safflower oil, polypropylene glycol and other natural oils.
  • Typical release rate modifiers include oleic, stearic, palmitic and other saturated or unsaturated fatty acids; cholic acid, diacylphosphoric acid and other hydrophobic anionic compounds; phospholipids, diesters of citric acid, benzoic acid, substituted benzoic acids, substituted phenols, ion exchange polymers, EudragitTM, methacrylate-methacrylic acid copolymers, TweensTM, SpansTM, lecithin, alkyl nitrates, ethyl or methyl cellulose.
  • a gel-in-place drug delivery system will include two components: the gelling components containing the phase change material and, optionally, a rheology modifier; and the drug release component containing the drug, carrier and, optionally, a release rate modifier.
  • the drug release rate may also be regulated by the carrier per se when there is a chemical affinity of the drug to the carrier.
  • a release rate modifier may be incorporated into the carrier, forming complexes or conjugates of carrier and modifier, and the like.
  • the drug release component may also comprise a drug unmodified by release modifiers.
  • a component for example, may comprise the drug dispersed in a solid lipophilic system such as anionic wax, self-emulsifying wax, cholesterol, fatty acid esters, beeswax or tallow.
  • a reservoir device such as that shown in Figures 1 or 2 may be utilized where the reservoir can contain a much larger dose of drug compared to, for example, the filament configuration.
  • a gel is used to provide sustained delivery of the drug it can be readily sterilized during preparation, then aseptically loaded into a sterile delivery device. Gels may be formulated as low viscosity dispersions with the drug or drug carrier which, when in contact with urine in the bladder, then gel or precipitate to form a solid filament or mass, thereby forming a delivery vehicle which can be retained in the bladder.
  • the device must have a configuration, not limited to those disclosed, such that it does not block the flow of urine from the bladder or cause excessive mechanical irritation to the bladder wall.
  • a configuration not limited to those disclosed, such that it does not block the flow of urine from the bladder or cause excessive mechanical irritation to the bladder wall.
  • a solution of oxybutynin chloride (titer: 50 mg/ml) (1 ml) and 2% collagen (50 grams) is homogeneously mixed with stirring while preventing occurrence of foam.
  • the mixture is lyophilized and pulverized at a low temperature using liquid nitrogen.
  • the pulverized product is formed under compression to give a needle- shaped preparation.
  • EXAMPLE 2 Materials of Example 1 are prepared with the addition of glycerol in order to impart flexibility to the device. The mixture is extruded into a filament and then dried. The filament may be randomly wound and inserted through a catheter for insertion into the bladder . EXAMPLE 3
  • EXAMPLE 4 Preparation of Drug Containing Emulsion
  • a 100 ml plastic beaker 1.25 grams of oleic acid is combined with 3.75 grams of purified corn oil.
  • 0.25 grams of Tween 80 is added and mixed well.
  • a rotor stator type high shear mixer (Virtis, Cyclone)
  • 42.25 ml of water is slowly added to the blend. The mixing is continued throughout the addition process and for an additional minute once the addition of the water is complete.
  • the resulting emulsion is mixed with a magnetic stir bar.
  • DL-polylactic acid (5 grams) is dissolved in dichloromethane (95 grams) with gentle mixing. Oxybutynin chloride (2.5 grams) is then added to the polymer solution and dissolved. The drug/polymer solution is spray-dried in a spray drier (Yamato) to yield hollow drug loaded polylactic acid microspheres .
  • the filtered solution of gellan gum/polyacrylic acid solution (example 3) is added into a 200 ml beaker.
  • microspheres (5 grams from example 5) are dispersed into 50 ml deionized water containing 0.25% Pluronic ® F-127.
  • the filtered solution of 1% gellan gum solution (example 1) is placed into a 200 ml beaker and warmed to approximately 40 °C.
  • the mixing head of the overhead mixer is placed into the beaker to begin agitation.
  • the drug containing microsphere solution is slowly added to the gum solution. Mixing is continued for an additional 3 minutes after addition is complete.
  • the solution is cooled to room temperature. Aliquots of 1 ml of the microsphere/gum dispersion are placed into 5 ml lyophilization vials, lyophilized and stored under vacuum.
  • the solution of gellan gum solution (a) is added into a 200 ml beaker.
  • the solution is warmed to approximately 40 °C.
  • the mixing head of the overhead mixer is placed into the beaker to begin agitation.
  • the drug containing emulsion (b) is added slowly to the gum solution. Mixing is continued for an additional 3 minutes after addition is complete.
  • the solution is cooled to room temperature.
  • the pH is adjusted to 6.5 with IN HC1 or NaOH as necessary.
  • a sample of 0.25 grams of the desired delivery system (a 3% oxybutynin system is used unless otherwise indicated) is introduced into 250 mL of an artificial urine (composed of 500 mM solution of sodium chloride containing 50 mM phosphate buffer) via an 18 gage cannula.
  • the pH of the elution buffer is 6.2 unless otherwise listed. Aliquots of the elution buffer are collected at the indicated times during a 24 hour period and analyzed by high performance liquid chromatography .
  • the system was introduced into the buffer using a 18 gage cannula (0.8 mm diameter) as described above and into a second buffer system using a 3 mm diameter cannula. Drug release from each system was determined and plotted as a fraction of the total drug introduced into the system. The drug release was observed to be slower from the system delivered from the 3 mm cannula. See FIG. 7.
  • Release study 3 Effect of Varying Drug Content Release studies were conducted on the two systems described above (A and B) . In this case, rather than sampling the buffer over a 24 hour period, the buffer was sampled every 24 hours and immediately was exchanged with fresh buffer to model the release over several days. A greater amount of drug was released from the 3% oxybutynin system than was released from the 1% oxybutynin system. The amount released from the 3% system was observed to be more consistent over the nine buffer exchanges than the amount released from the 1% system which released fractionally more drug early in the study. See FIG. 8. Release Study 4: Effect of Modifier Concentration
  • Formulations containing 0, 3, 6.25 and 12.5% wt/wt oleic acid were prepared as described above, except that the appropriate amount of oleic acid was used. Release studies were conducted on each formulation and the amount of drug release was determined and plotted in FIG. 9 as the concentration in the buffer versus time. It was observed that less drug is released from the system as the modifier concentration is increased.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Urology & Nephrology (AREA)
  • Inorganic Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Gynecology & Obstetrics (AREA)
  • Reproductive Health (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Infusion, Injection, And Reservoir Apparatuses (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur des préparations bioérodables à libération continue s'introduisant dans la vessie par l'urètre et y libérant des médicaments. Elles se présentent sous forme de filaments, de timbres ou de gel fluide s'introduisant à l'aide d'un cathéter. Le dispositif s'érode biologiquement pendant ou après la libération continue du médicament de manière à ne pas obstruer les voies urinaires pendant qu'il est en place dans la vessie.
PCT/US1998/006445 1997-04-03 1998-04-02 Systeme intravesical de liberation de medicaments Ceased WO1998043555A1 (fr)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CA002285591A CA2285591A1 (fr) 1997-04-03 1998-04-02 Systeme intravesical de liberation de medicaments
DE19882286T DE19882286T1 (de) 1997-04-03 1998-04-02 Intravesikale Medikamentenabgabesysteme
JP54197098A JP2001519787A (ja) 1997-04-03 1998-04-02 膀胱内ドラッグデリバリーシステム
AU68764/98A AU6876498A (en) 1997-04-03 1998-04-02 Intravesical drug delivery system
EP98914404A EP0971641A4 (fr) 1997-04-03 1998-04-02 Systeme intravesical de liberation de medicaments
GB9923410A GB2338414B (en) 1997-04-03 1998-04-02 Intravesical drug delivery system
KR1019997009105A KR20010006027A (ko) 1997-04-03 1998-04-02 방광내 약물 송달 시스템
NO994837A NO994837L (no) 1997-04-03 1999-10-04 Intravesikal medikamentavleveringssystem

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US83324797A 1997-04-03 1997-04-03
US08/833,247 1997-04-03

Publications (1)

Publication Number Publication Date
WO1998043555A1 true WO1998043555A1 (fr) 1998-10-08

Family

ID=25263865

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/006445 Ceased WO1998043555A1 (fr) 1997-04-03 1998-04-02 Systeme intravesical de liberation de medicaments

Country Status (10)

Country Link
US (3) US6039967A (fr)
EP (1) EP0971641A4 (fr)
JP (1) JP2001519787A (fr)
KR (1) KR20010006027A (fr)
AU (1) AU6876498A (fr)
CA (1) CA2285591A1 (fr)
DE (1) DE19882286T1 (fr)
GB (1) GB2338414B (fr)
NO (1) NO994837L (fr)
WO (1) WO1998043555A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999048494A1 (fr) * 1998-03-26 1999-09-30 Alza Corporation Composition d'oxybutine a liberation continue et effet de xerostomie reduit
WO2000074650A3 (fr) * 1999-06-04 2001-07-05 Alza Corp Compositions de gel implantables et procede de fabrication
EP1553899A4 (fr) * 2002-10-22 2006-10-25 Procede et systeme d'administration intravasculaire d'agents therapeutiques
EP1165048A4 (fr) * 1999-04-06 2007-12-05 Lipocine Inc Compositions et procedes d'administration amelioree d'agents therapeutiques hydrophobes ionisables
DE102007003765A1 (de) * 2007-01-19 2008-07-24 Farco-Pharma Gmbh Pharmazeutische Zusammensetzung zur Behandlung von Inkontinenz
EP1691718A4 (fr) * 2003-12-11 2010-07-07 Gore Enterprise Holdings Inc Microparticules therapeutiques
DE102009035586A1 (de) 2009-07-31 2011-02-03 Fresenius Kabi Deutschland Gmbh Intravesikale Instillationslösungen zur Behandlung von Blasenkrebs
WO2010129331A3 (fr) * 2009-04-28 2011-02-17 Ams Research Corporation Système et procédé de traitement biologique
EP1949890A3 (fr) * 1999-06-04 2011-05-18 ALZA Corporation Compositions de gel implantables et procédé de fabrication
WO2011084712A1 (fr) * 2009-12-17 2011-07-14 Taris Biomedical, Inc. Dispositif implantable doté d'une tolérance intravésicale et procédés de traitement
WO2012048114A1 (fr) * 2010-10-06 2012-04-12 Taris Biomedical, Inc. Systèmes et procédés d'administration de médicament biorésorbables ou rétractables sélectifs dans le temps
CN103861091A (zh) * 2014-03-20 2014-06-18 辽宁亿灵科创生物医药科技有限公司 治疗膀胱炎的药物组合物
AU2015201123B2 (en) * 2009-12-17 2016-04-21 Taris Biomedical Llc Implantable device with intravesical tolerability and methods of treatment
US10617657B2 (en) 2011-01-10 2020-04-14 Allergan, Inc. Devices and methods for sustained treatment of bladder pain and irritative voiding

Families Citing this family (110)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6214331B1 (en) * 1995-06-06 2001-04-10 C. R. Bard, Inc. Process for the preparation of aqueous dispersions of particles of water-soluble polymers and the particles obtained
US6623751B2 (en) * 1998-07-30 2003-09-23 L'oreal S.A. Cosmetic, pharmaceutical, or dermatological patch
US6293923B1 (en) 1999-03-15 2001-09-25 Innoventions, Inc. Intravesicular balloon
US6527718B1 (en) 1999-08-20 2003-03-04 Brian G Connor Ultrasound system for continuous imaging and delivery of an encapsulated agent
US6740039B1 (en) 1999-08-20 2004-05-25 Koninklijke Philips Electronics N.V. Methods and apparatus for displaying information relating to delivery and activation of a therapeutic agent using ultrasound energy
US7029694B2 (en) * 2000-04-26 2006-04-18 Watson Laboratories, Inc. Compositions and methods for transdermal oxybutynin therapy
US7179483B2 (en) * 2000-04-26 2007-02-20 Watson Pharmaceuticals, Inc. Compositions and methods for transdermal oxybutynin therapy
US20030124177A1 (en) * 2000-04-26 2003-07-03 Watson Pharmaceuticals, Inc. Compositions and methods for transdermal oxybutynin therapy
JP2003531157A (ja) * 2000-04-26 2003-10-21 ワトソン ファーマシューティカルズ， インコーポレイテッド オキシブチニン治療に関連した有害な経験の最小化
US6398718B1 (en) 2000-06-15 2002-06-04 Innoventions, Inc. Intravesicular device
US6545046B2 (en) 2000-08-30 2003-04-08 Theramax Inc. Method for enhanced delivery of oxybutynin and compositions thereof
US6699665B1 (en) * 2000-11-08 2004-03-02 Surface Logix, Inc. Multiple array system for integrating bioarrays
AU2002254167A1 (en) * 2001-03-13 2002-09-24 Clemson University Intraurethral device for treating or detecting various diseases or infections of the urinary system
US6558312B2 (en) 2001-03-13 2003-05-06 Clemson University Intraurethral device for incontinence
KR100426636B1 (ko) * 2001-05-18 2004-04-08 한국과학기술연구원 주사 가능한 젤 상의 조성물 및 그의 제조방법
US6702744B2 (en) * 2001-06-20 2004-03-09 Advanced Cardiovascular Systems, Inc. Agents that stimulate therapeutic angiogenesis and techniques and devices that enable their delivery
US8110217B2 (en) * 2001-08-13 2012-02-07 University Of Pittsburgh Sphingomyelin liposomes for the treatment of hyperactive bladder disorders
WO2003015698A2 (fr) * 2001-08-13 2003-02-27 University Of Pittsburgh Application de vehicules lipidiques et utilisation dans le cadre de l'administration de medicaments
US6878693B2 (en) 2001-09-28 2005-04-12 Solubest Ltd. Hydrophilic complexes of lipophilic materials and an apparatus and method for their production
US20050233003A1 (en) * 2001-09-28 2005-10-20 Solubest Ltd. Hydrophilic dispersions of nanoparticles of inclusion complexes of salicylic acid
US20050227911A1 (en) * 2001-09-28 2005-10-13 Solubest Ltd. Hydrophilic dispersions of nanoparticles of inclusion complexes of macromolecules
US6893431B2 (en) 2001-10-15 2005-05-17 Scimed Life Systems, Inc. Medical device for delivering patches
US8563592B2 (en) 2001-11-01 2013-10-22 Spectrum Pharmaceuticals, Inc. Bladder cancer treatment and methods
CA2789114C (fr) 2001-11-01 2014-03-25 Spectrum Pharmaceuticals, Inc. Compositions medicales pour le traitement intravesical du cancer de la vessie
US7700851B2 (en) * 2001-11-13 2010-04-20 U.S. Smokeless Tobacco Company Tobacco nicotine demethylase genomic clone and uses thereof
US8608661B1 (en) 2001-11-30 2013-12-17 Advanced Cardiovascular Systems, Inc. Method for intravascular delivery of a treatment agent beyond a blood vessel wall
US8685427B2 (en) 2002-07-31 2014-04-01 Boston Scientific Scimed, Inc. Controlled drug delivery
US8133501B2 (en) 2002-02-08 2012-03-13 Boston Scientific Scimed, Inc. Implantable or insertable medical devices for controlled drug delivery
US7361368B2 (en) 2002-06-28 2008-04-22 Advanced Cardiovascular Systems, Inc. Device and method for combining a treatment agent and a gel
US8920826B2 (en) * 2002-07-31 2014-12-30 Boston Scientific Scimed, Inc. Medical imaging reference devices
US7149874B2 (en) * 2002-08-16 2006-12-12 Micron Technology, Inc. Memory hub bypass circuit and method
US7597903B2 (en) * 2002-12-02 2009-10-06 Shenkar College Of Engineering And Design Method and composition for producing catheters with antibacterial property
WO2004052440A1 (fr) * 2002-12-11 2004-06-24 Coloplast A/S Appareil de catheterisme urinaire a composition pharmaceutiquement active
JP2004246317A (ja) * 2002-12-20 2004-09-02 Hitachi Ltd 冷陰極型フラットパネルディスプレイ
US7544192B2 (en) 2003-03-14 2009-06-09 Sinexus, Inc. Sinus delivery of sustained release therapeutics
US8383158B2 (en) 2003-04-15 2013-02-26 Abbott Cardiovascular Systems Inc. Methods and compositions to treat myocardial conditions
US8038991B1 (en) 2003-04-15 2011-10-18 Abbott Cardiovascular Systems Inc. High-viscosity hyaluronic acid compositions to treat myocardial conditions
US8821473B2 (en) * 2003-04-15 2014-09-02 Abbott Cardiovascular Systems Inc. Methods and compositions to treat myocardial conditions
CN101193623A (zh) 2003-05-15 2008-06-04 柏尔迈瑞克斯公司 可植入的网状弹性基质的制造和应用
US20040249364A1 (en) * 2003-06-03 2004-12-09 Ilya Kaploun Device and method for dispensing medication to tissue lining a body cavity
CA2533165A1 (fr) * 2003-07-21 2005-01-27 Bio-Dar Ltd. Formes dosifiees a liberation controlee a base de gomme gellane a administrer par voie orale, une nouvelle technologie pour la retention gastrique
NZ528648A (en) 2003-10-02 2005-08-26 Agres Ltd Altering animal waste composition
US7763077B2 (en) 2003-12-24 2010-07-27 Biomerix Corporation Repair of spinal annular defects and annulo-nucleoplasty regeneration
WO2006013851A1 (fr) * 2004-08-03 2006-02-09 Nippon Shinyaku Co., Ltd. Dispositif a utiliser dans une cavite du corps et preparation a liberation continue
US8361490B2 (en) * 2004-09-16 2013-01-29 Theracoat Ltd. Biocompatible drug delivery apparatus and methods
US7854944B2 (en) 2004-12-17 2010-12-21 Advanced Cardiovascular Systems, Inc. Tissue regeneration
MX2007012324A (es) 2005-04-04 2008-02-12 Sinexus Inc Dispositivo y metodo para tratar condiciones del seno paranasal.
US20080125745A1 (en) * 2005-04-19 2008-05-29 Shubhayu Basu Methods and compositions for treating post-cardial infarction damage
US9539410B2 (en) 2005-04-19 2017-01-10 Abbott Cardiovascular Systems Inc. Methods and compositions for treating post-cardial infarction damage
US8828433B2 (en) 2005-04-19 2014-09-09 Advanced Cardiovascular Systems, Inc. Hydrogel bioscaffoldings and biomedical device coatings
US8187621B2 (en) * 2005-04-19 2012-05-29 Advanced Cardiovascular Systems, Inc. Methods and compositions for treating post-myocardial infarction damage
US8303972B2 (en) * 2005-04-19 2012-11-06 Advanced Cardiovascular Systems, Inc. Hydrogel bioscaffoldings and biomedical device coatings
CA2653541C (fr) 2005-06-06 2014-12-23 The University Of British Columbia Substitut de serum albumine a base de polymere
DK1933810T3 (da) * 2005-08-11 2013-01-28 Childrens Medical Center Intravesikal lægemiddelafgivelsesindretning og fremgangsmåde
US7732190B2 (en) * 2006-07-31 2010-06-08 Advanced Cardiovascular Systems, Inc. Modified two-component gelation systems, methods of use and methods of manufacture
US9242005B1 (en) 2006-08-21 2016-01-26 Abbott Cardiovascular Systems Inc. Pro-healing agent formulation compositions, methods and treatments
WO2008035172A2 (fr) * 2006-09-18 2008-03-27 Glenmark Pharmaceuticals Limited Composition pharmaceutique contenant de la desmopressine
US9005672B2 (en) * 2006-11-17 2015-04-14 Abbott Cardiovascular Systems Inc. Methods of modifying myocardial infarction expansion
US8741326B2 (en) * 2006-11-17 2014-06-03 Abbott Cardiovascular Systems Inc. Modified two-component gelation systems, methods of use and methods of manufacture
US8192760B2 (en) 2006-12-04 2012-06-05 Abbott Cardiovascular Systems Inc. Methods and compositions for treating tissue using silk proteins
US20080161639A1 (en) * 2006-12-28 2008-07-03 Olympus Medical Systems Corporation Capsule medical apparatus and body-cavity observation method
US8702591B2 (en) * 2007-01-12 2014-04-22 Olympus Medical Systems Corp. Capsule medical apparatus
EP2231254B9 (fr) 2007-12-11 2015-04-08 Massachusetts Institute of Technology Dispositif implantable d'administration de médicaments
CN101945621B (zh) 2007-12-18 2014-06-18 因特尔赛克特耳鼻喉公司 自扩展装置及用于其的方法
CA2732355A1 (fr) 2008-08-01 2010-02-04 Intersect Ent, Inc. Procedes et dispositifs pour sertir des dispositifs auto-dilatables
KR101689786B1 (ko) * 2008-08-09 2016-12-26 메사츄세츠 인스티튜트 어브 테크놀로지 남성 비뇨생식기 및 주위 조직을 치료하는 방법 및 체내이식형 약물 전달 장치
US20100291182A1 (en) * 2009-01-21 2010-11-18 Arsenal Medical, Inc. Drug-Loaded Fibers
CA3031836A1 (fr) 2009-05-05 2010-11-11 Board Of Regents, The University Of Texas System Formulations d'anesthesiques volatils pour reduire l'inflammation
CN102573981B (zh) 2009-05-15 2016-06-22 因特尔赛克特耳鼻喉公司 可展开装置及其使用方法
CN101724163B (zh) * 2009-06-23 2011-09-07 河南科技大学 一种壳聚糖衍生物复合微球及其制备方法和应用
CA2765734C (fr) 2009-06-26 2016-12-13 Taris Biomedical, Inc. Dispositifs implantables d'administration de medicament et leurs procedes de fabrication
US9173817B2 (en) 2009-08-24 2015-11-03 Arsenal Medical, Inc. In situ forming hemostatic foam implants
US10420862B2 (en) 2009-08-24 2019-09-24 Aresenal AAA, LLC. In-situ forming foams for treatment of aneurysms
US9044580B2 (en) 2009-08-24 2015-06-02 Arsenal Medical, Inc. In-situ forming foams with outer layer
US20110202016A1 (en) * 2009-08-24 2011-08-18 Arsenal Medical, Inc. Systems and methods relating to polymer foams
US9017312B2 (en) 2009-09-10 2015-04-28 Taris Biomedical Llc Implantable device for controlled drug delivery
ES2732150T3 (es) 2010-01-20 2019-11-20 Urogen Pharma Ltd Material y método para tratar cavidades internas
CA2999629C (fr) 2010-03-01 2020-12-15 The University Of British Columbia Polyglycerols hyper-ramifies substitues
EP3711750B1 (fr) 2010-08-05 2023-09-06 TARIS Biomedical LLC Dispositifs implantables d'administration de médicaments pour des sites génito-urinaires
US8968626B2 (en) 2011-01-31 2015-03-03 Arsenal Medical, Inc. Electrospinning process for manufacture of multi-layered structures
US9034240B2 (en) 2011-01-31 2015-05-19 Arsenal Medical, Inc. Electrospinning process for fiber manufacture
US9194058B2 (en) 2011-01-31 2015-11-24 Arsenal Medical, Inc. Electrospinning process for manufacture of multi-layered structures
US9107816B2 (en) 2011-02-04 2015-08-18 Taris Biomedical Llc Implantable device for controlled dissolution and diffusion of low solubility drug
US8476221B2 (en) 2011-03-18 2013-07-02 Halimed Pharmaceuticals, Inc. Methods and compositions for the treatment of metabolic disorders
EP2734187B1 (fr) 2011-07-20 2018-09-05 UroGen Pharma Ltd. Matériaux et méthode de traitement de cavités corporelles internes
JP6495654B2 (ja) 2011-10-24 2019-04-03 アサナ バイオサイエンシズ，リミティド ライアビリティ カンパニー シクロヘキシルアミン類
US8993831B2 (en) 2011-11-01 2015-03-31 Arsenal Medical, Inc. Foam and delivery system for treatment of postpartum hemorrhage
CN112169134B (zh) 2012-05-19 2022-11-29 塔里斯生物医药公司 具有改良取回特征的可植入泌尿器械
JP6399663B2 (ja) 2013-03-14 2018-10-03 インターセクト エント， インコーポレイテッド 副鼻腔状態を処置するためのシステム、デバイスおよび方法
EP2968880B1 (fr) 2013-03-15 2025-04-30 TARIS Biomedical LLC Dispositifs d'administration de médicament dotés d'un composant étanche aux médicaments
IL299897B2 (en) 2013-08-19 2024-02-01 Taris Biomedical Llc Devices and methods for administering multiple units of drug
EP3083619B1 (fr) 2013-12-16 2021-11-03 Asana BioSciences, LLC Composés de p2x3 et/ou p2x2/3 et procédés
JP6856380B2 (ja) 2014-06-26 2021-04-07 タリス バイオメディカル エルエルシー 弾性ポリマー−薬物マトリックス系を含む膀胱内薬物送達デバイス及び方法
CZ308594B6 (cs) * 2014-09-29 2020-12-23 VÝZKUMNÝ ÚSTAV VETERINÁRNÍHO LÉKAŘSTVÍ, v.v.i. Mukoadhezivní nosiče částic, způsob přípravy a použití
CA2974376A1 (fr) 2015-01-22 2016-07-28 Intersect Ent, Inc. Ballonnet enduit de medicament
WO2016172704A1 (fr) 2015-04-23 2016-10-27 Taris Biomedical Llc Dispositifs d'administration de médicaments dotés d'un composant perméable aux médicaments et procédés associés
BR112019006216A2 (pt) 2016-09-30 2019-06-25 Asana Biosciences Llc compostos de p2x3 e/ou p2x2/3 e métodos
US20180256867A1 (en) * 2017-03-07 2018-09-13 Bruce H. Levin Nasal Delivery Device and Methods of Use
IT201700104446A1 (it) 2017-09-19 2019-03-19 Lo Li Pharma Srl Compositions, uses and methods for treatment of infertility and subfertility
WO2019122119A1 (fr) 2017-12-22 2019-06-27 Lo.Li. Pharma International S.R.L. Traitement de la fibrose avec de l'inositol
EP3856143A4 (fr) * 2018-09-27 2022-07-06 Watershed Medical, Inc. Dispositif et procédé de traitement d'infections
WO2020168244A1 (fr) 2019-02-15 2020-08-20 Incelldx, Inc. Dosage d'échantillons associés à la vessie, identification et traitement d'une néoplasie associée à la vessie, et kits destinés à être utilisés dans ces derniers
IT201900003843A1 (it) 2019-03-15 2020-09-15 Lo Li Pharma Srl Trattamento di fibromi con vitamina D e un agente come l'epigallocatechina gallato (EGCG)
US20220211615A1 (en) * 2019-04-30 2022-07-07 Trigone Pharma Ltd. Formulations and methods for drug instillation into the bladder and treatment of bladder ailments
EP3952973B1 (fr) 2019-06-13 2023-06-07 Hollister Incorporated Produits de type cathéter urinaire réutilisable
EP4628107A2 (fr) 2019-06-25 2025-10-08 Hollister Incorporated Produits pour sondes urinaires réutilisables
US12403291B2 (en) 2019-08-30 2025-09-02 Intersect Ent, Inc. Submucosal bioresorbable drug eluting platform
US20210100950A1 (en) 2019-10-02 2021-04-08 Watershed Medical, Inc. Device and method for improving retention of a therapy in the bladder
IL316407A (en) * 2022-04-19 2024-12-01 Watershed Medical Inc A preparation for the treatment of urinary system disorders
IT202200013867A1 (it) 2022-06-30 2023-12-30 Lo Li Pharma Srl Composizione per il trattamento dell’ infezione da papilloma virus (hpv)

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2961374A (en) * 1950-10-14 1960-11-22 Lieb Hans Injectable pharmaceutical preparation, and a method of making same
JPS51140582A (en) * 1975-05-30 1976-12-03 Nec Corp Semiconductor resistance element
US4774091A (en) * 1983-10-14 1988-09-27 Sumitomo Pharmaceuticals Company, Ltd. Long-term sustained-release preparation
FR2588189B1 (fr) * 1985-10-03 1988-12-02 Merck Sharp & Dohme Composition pharmaceutique de type a transition de phase liquide-gel
US4871542A (en) * 1987-04-30 1989-10-03 Ferring Service Center, N.V. Method and apparatus useful for delivering medicinal compositions into the bladder and urinary tract
FR2657018A1 (fr) * 1990-01-12 1991-07-19 Merck Sharp & Dohme Composition ophtalmique fluide a base de microparticules lipidiques contenant au moins un principe actif et son procede de preparation.
WO1991017745A1 (fr) * 1990-05-23 1991-11-28 Southwest Research Institute Systeme a filament d'acheminement d'un medicament et procede
EP0572932B1 (fr) * 1992-06-02 2000-09-13 C.R. Bard, Inc. Procédé et dispositif implantable pour la délivrance à long terme de médicaments

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
OKADO M, ET AL.: "STUDY ON INTRAVESICAL STICK DEVELOPMENT OF INTRAVESICAL STICK AND ITS INSTLLATOR", STUDY ON INTRAVESICAL STICK, XX, XX, vol. 76, no. 02, 1 January 1985 (1985-01-01), XX, pages 157 - 203 + 02, XP002912597 *
See also references of EP0971641A4 *

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999048494A1 (fr) * 1998-03-26 1999-09-30 Alza Corporation Composition d'oxybutine a liberation continue et effet de xerostomie reduit
EP1165048A4 (fr) * 1999-04-06 2007-12-05 Lipocine Inc Compositions et procedes d'administration amelioree d'agents therapeutiques hydrophobes ionisables
EP1949890A3 (fr) * 1999-06-04 2011-05-18 ALZA Corporation Compositions de gel implantables et procédé de fabrication
JP2003501375A (ja) * 1999-06-04 2003-01-14 アルザ・コーポレーション 移植可能なゲル組成物および製造方法
CN100370967C (zh) * 1999-06-04 2008-02-27 阿尔萨公司 埋植凝胶组合物及其制备方法
AU779277B2 (en) * 1999-06-04 2005-01-13 Alza Corporation Implantable gel compositions and method of manufacture
WO2000074650A3 (fr) * 1999-06-04 2001-07-05 Alza Corp Compositions de gel implantables et procede de fabrication
EP1553899A4 (fr) * 2002-10-22 2006-10-25 Procede et systeme d'administration intravasculaire d'agents therapeutiques
EP1691718A4 (fr) * 2003-12-11 2010-07-07 Gore Enterprise Holdings Inc Microparticules therapeutiques
DE102007003765A1 (de) * 2007-01-19 2008-07-24 Farco-Pharma Gmbh Pharmazeutische Zusammensetzung zur Behandlung von Inkontinenz
WO2008086834A3 (fr) * 2007-01-19 2008-09-18 Farco Gmbh Composition pharmaceutique pour le traitement de l'incontinence
US8974368B2 (en) 2009-04-28 2015-03-10 Ams Research Corporation Pelvic tissue support devices
US9925302B2 (en) 2009-04-28 2018-03-27 Boston Scientific Scimed, Inc. Biologic treatment system and method
WO2010129331A3 (fr) * 2009-04-28 2011-02-17 Ams Research Corporation Système et procédé de traitement biologique
DE102009035586A1 (de) 2009-07-31 2011-02-03 Fresenius Kabi Deutschland Gmbh Intravesikale Instillationslösungen zur Behandlung von Blasenkrebs
WO2011084712A1 (fr) * 2009-12-17 2011-07-14 Taris Biomedical, Inc. Dispositif implantable doté d'une tolérance intravésicale et procédés de traitement
AU2010339821B2 (en) * 2009-12-17 2015-02-19 Taris Biomedical Llc Implantable device with intravesical tolerability and methods of treatment
AU2015201123B2 (en) * 2009-12-17 2016-04-21 Taris Biomedical Llc Implantable device with intravesical tolerability and methods of treatment
EP3884988A1 (fr) * 2009-12-17 2021-09-29 TARIS Biomedical LLC Dispositif implantable doté d'une tolérance intravésicale et procédés de traitement
US11890439B2 (en) 2009-12-17 2024-02-06 Taris Biomedical Llc Drug delivery device with intravesical tolerability
WO2012048114A1 (fr) * 2010-10-06 2012-04-12 Taris Biomedical, Inc. Systèmes et procédés d'administration de médicament biorésorbables ou rétractables sélectifs dans le temps
US10617657B2 (en) 2011-01-10 2020-04-14 Allergan, Inc. Devices and methods for sustained treatment of bladder pain and irritative voiding
CN103861091A (zh) * 2014-03-20 2014-06-18 辽宁亿灵科创生物医药科技有限公司 治疗膀胱炎的药物组合物
CN103861091B (zh) * 2014-03-20 2016-04-27 辽宁亿灵科创生物医药科技有限公司 治疗膀胱炎的药物组合物

Also Published As

Publication number Publication date
GB2338414B (en) 2001-12-19
US20010019719A1 (en) 2001-09-06
AU6876498A (en) 1998-10-22
KR20010006027A (ko) 2001-01-15
NO994837L (no) 1999-11-10
JP2001519787A (ja) 2001-10-23
EP0971641A1 (fr) 2000-01-19
CA2285591A1 (fr) 1998-10-08
EP0971641A4 (fr) 2003-08-13
US6039967A (en) 2000-03-21
GB9923410D0 (en) 1999-12-08
DE19882286T1 (de) 2000-04-27
NO994837D0 (no) 1999-10-04
US6524608B2 (en) 2003-02-25
GB2338414A (en) 1999-12-22
US6207180B1 (en) 2001-03-27

Similar Documents

Publication Publication Date Title
US6524608B2 (en) Intravesical drug delivery system
JP4330175B2 (ja) 高粘度液体による制御された送達系
JP3941878B2 (ja) 生物分解性放出制御溶融紡糸デリバリーシステム
CN100522244C (zh) 高粘度液体受控输送体系
Jalil et al. Biodegradable poly (lactic acid) and poly (lactide-co-glycolide) microcapsules: problems associated with preparative techniques and release properties
EP0102265B1 (fr) Formulation injectable de microparticules à effet prolongé pour l'administration d'agents anti-inflammatoires
CA2338605C (fr) Systeme d'administration polymerique souple et moulable d'agents bioactifs
AU762677B2 (en) Prolonged release bioadhesive vaginal gel dosage form
EP1797873A2 (fr) Microparticules compressées pour injection sèche
Wu et al. Long-acting injectable hormonal dosage forms for contraception
JP2001516728A (ja) デバイスとしての高粘性液状コントロールドデリバリーシステム
JP2009509982A (ja) 内耳疾患を治療するための医薬品組成物
WO1997010826A1 (fr) Composition pharmaceutique
JP4073478B2 (ja) 生物分解性制御放出型微細球およびその製法
PT950403E (pt) Emulsões para sistemas de libertação in situ
JPS6323815A (ja) 徐放性薬物含有繊維
JP4918212B2 (ja) 徐放性軟カプセル剤用の液体組成物およびこれらの製造方法
CA2569542C (fr) Systeme de liberation
CN101478955A (zh) 包含胶体二氧化硅的丸剂
JPH04124127A (ja) マイクロカプセル型徐放性製剤及びその製造法
WO1999030683A1 (fr) Preparation a temps de sejour prolonge dans la zone d'application
ES2365502T3 (es) Preparación farmacéutica de liberación prolongada y método para administrarla.
JP2011500688A (ja) 制御された嵩密度を有する生分解性インプラント
JPH041124A (ja) 眼用懸濁液
TAMANNA 5. ADVANCES IN LONG ACTING DRUG PREPARATIONS IN VETERINARY PRACTICE by SOLANKI TAMANNA, H1., GONDALIYA, VAISHALI1, TANVI D. MANAT2, PATEL, SA 3 AND PANDYA, SHAILEE4

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH GM GW HU ID IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG UZ VN YU ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
ENP Entry into the national phase

Ref document number: 2285591

Country of ref document: CA

Ref document number: 2285591

Country of ref document: CA

Kind code of ref document: A

Ref document number: 1998 541970

Country of ref document: JP

Kind code of ref document: A

Ref document number: 9923410

Country of ref document: GB

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 1019997009105

Country of ref document: KR

WWE Wipo information: entry into national phase

Ref document number: 1998914404

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1998914404

Country of ref document: EP

RET De translation (de og part 6b)

Ref document number: 19882286

Country of ref document: DE

Date of ref document: 20000427

WWE Wipo information: entry into national phase

Ref document number: 19882286

Country of ref document: DE

WWP Wipo information: published in national office

Ref document number: 1019997009105

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1019997009105

Country of ref document: KR